Eales Disease 

Eales Disease – Introduction

• Eales disease is a rare, idiopathic, often bilateral occlusive vasculitis of the peripheral retina characterized by 3 overlapping stages of venous inflammation, vascular occlusion, and retinal neovascularization.^(1,2,3)
• If the macula is involved (uncommon), it is referred to as central Eales disease.⁽³⁾
• The clinical course of Eales disease is highly variable, with some patients progressing to complete vision loss and others experiencing temporary or permanent remission.⁽³⁾

Synonyms

• Eales’ disease
• Eales’ retinopathy
• Idiopathic peripheral periphlebitis
• Idiopathic retinal periphlebitis

Epidemiology

Geographic Distribution

• Eales disease is most commonly found in the Indian subcontinent, and is rarely seen in the United States, Canada, and the United Kingdom.^(1,3)

Incidence/Prevalence

• Most cases of Eales disease are reported in healthy male adults aged 20-30 years.⁽³⁾
• Reported incidence in India:
  • 1 in 200-250 ophthalmic patients presenting to general eye hospital⁽³⁾
  • 1 in 135 ophthalmic patients presenting to referral ophthalmic center (Ocul Immunol Inflamm 2018;26(6):870)

Risk Factors

• Risk factors for Eales disease have not been clearly identified, but increased rates in low income countries compared to high income countries may potentially be related to poor nutrition, environmental factors, and overall patient health.⁽³⁾

Etiology and Pathogenesis

Causes

• The exact cause of Eales disease is unknown but thought to be immune-related, potentially due to immunologic response to Mycobacterium tuberculosis antigens and hypersensitivity to tuberculoprotein.^(1,2,3)

Pathogenesis

• The pathogenesis of Eales disease is not fully understood but appears to be multifactorial.^(2,3)
• Eales disease is characterized by 3 overlapping phases.
  • The early inflammatory phase includes peripheral to mid-peripheral periphlebitis, venous dilation, and perivascular exudate.
  • The intermediate ischemic phase is characterized by retinal capillary nonperfusion and ischemia with a distinct junction of perfused and nonperfused retina marked by arteriovenous shunts, venous beading, and microaneurysms.
  • The late proliferative phase is characterized by neovascularization (retinal new vessels and disc new vessels) proximal to the junction of perfused and nonperfused retina.
    • Retinal new vessels may lead to recurrent vitreous hemorrhages and tractional retinal detachment.
    • Spontaneously regressing new vessels are replaced by glial tissue but may cause retinal traction and detachment.
    •  Rhegmatogenous retinal detachment, which may also occur, is caused by small tears, holes, or breaks in the retina leading to accumulation of vitreous in the subretinal space and detachment.
  • References – ^(1,3), American Academy of Ophthalmology 2021 Dec 4, N Engl J Med 2008 Nov 27;359(22):2346)
• In some patients with Eales disease, recanalization, venovenous capillary shunts, and tissue atrophy may lead to circulatory stabilization and resolution without recurrence.⁽³⁾
• Other patients have recurrent vitreous hemorrhage, which may occur through 3 pathways.⁽³⁾
  • Acute phlebitis with rapid venous flow obstruction may result in a large vitreous hemorrhage that may not clear for months.
  • Phlebitis involving smaller peripheral venules may lead to venous obstruction with subacute closure and a small vitreous hemorrhage that is often absorbed, but repeated acute involvement of small-caliber venules may lead to repeated vitreous hemorrhage.
  • Most often, repeated vitreous hemorrhage occurs in patients with neovascularization resulting from persistent peripheral circulatory deficiency and retinal ischemia.
• Recurrent vitreous hemorrhages may result in traction bands and membranes forming within the vitreous, potentially resulting in total vision loss.⁽³⁾

History and Physical

History

Chief Concern (CC)

• Most patients with Eales disease present with vision loss or a decrease in visual acuity.^(1,3)
  • Vision loss is usually bilateral (reported in 50%-90% of patients).
  • Some patients may present with symptoms in 1 eye despite signs of disease in both eyes on examination.
• Some patients may report a minor reduction in visual acuity, with or without symptoms of recurrent vitreous hemorrhage (described as small specks, floaters, or cobwebs occluding the vision).^(1,3)
• Initial symptoms reported in retrospective cohort study of 500 patients (898 eyes) with Eales disease:
  • Decreased vision alone in 40% of eyes
  • Floaters with decreased vision in 28% of eyes
  • Floaters alone in 14% of eyes
  • No symptoms in 18% of eyes
  • Reference – Ocul Immunol Inflamm 2018;26(6):870

History of Present Illness (HPI)

• Ask about small specks, floaters, cobwebs, or a decrease in visual acuity in either or both eyes.^(1,3)

Past Medical History (PMH)

• Ask about known Mycobacterium tuberculosis infection or potential exposure.^(1,2,3)
• Ask about comorbidities and other vasculitides, although Eales disease most commonly occurs in healthy young adults (Ocul Immunol Inflamm 2018;26(6):870).

Physical

HEENT

• Perform an ocular exam, including visual acuity and visual field testing (AAO PPP 2022 DecPDF).
• Perform a fundoscopic retinal exam to assess for the 3 characteristic features of Eales disease, including vascular inflammation, peripheral nonperfusion, and retinal neovascularization.⁽³⁾
  • Vascular inflammation (retinal phlebitis):
    • Peripheral veins (phlebitis) are most often affected but arterioles may also have inflammation.
    • Fundoscopic exam findings include:
      • Midperipheral venous dilation
      • Perivascular exudate at the peripheral veins
      • Superficial retinal hemorrhages
      • Vascular sheathing, the appearance of which may range from thin white lines limiting the blood column on both sides to segmental heavy exudative sheathing
  • Peripheral nonperfusion:
    • Findings on fundoscopic exam include:
      •  Solid white lines on areas of nonperfusion (indicates obliterated large vessels)
      • Highly distinct junction between anterior peripheral nonperfusion and posterior perfused retina
    • Vascular abnormalities that may be found at the junction include:
      • Microaneurysm
      • Venovenous shunts
      • Venous beading
      • Hard exudate
      • Cotton-wool spots
  • Retinal neovascularization (reported in up to 80% of patients):
    • New vessel formation occurs on the disc or elsewhere (often on the junction between perfused and nonperfused retina).
    • Fundoscopic exam findings in patients with recurrent hemorrhage include:
      • Evidence of old blood
      • Signs of fibrous organization
      • Retinitis proliferans
      • Tractional retinal detachment
• Macular involvement (referred to as central Eales disease) is uncommon but can occur in patients with extensive disease and in later stages of proliferation.^(2,3)
  • Midperipheral lesions will be localized in the posterior pole.
  • Cystoid macular edema may cause reduction of vision in the early stage of the disease.

Table 1: Fundoscopic Exam Findings Reported in 2 Studies in Patients With Eales Disease

Exam Finding	In Cross-Sectional Study of 50 Patients (79 Eyes)	In Retrospective Cohort Study of 75 Patients (106 Eyes)
Neovascularization elsewhere in the retina (other than the optic disc)	65.8% of eyes	29.2% of eyes
Sclerosed vessels	50.6% of eyes	61.3% of eyes
Vitreous hemorrhage	36.7% of eyes	34.9% of eyes
Periphlebitis	34.2% of eyes	37.7% of eyes
Intra-retinal hemorrhage	29.1% of eyes	NA
Fibrovascular proliferation	25.3% of eyes	NA
Neovascularization of the optic disc	11.4% of eyes	NA
Tractional retinal detachment	5.1% of eyes	NA
Vitritis	NA	22.6% of eyes

• Staging at initial presentation in retrospective cohort study of 75 patients (106 eyes) with Eales disease:
  • 37.8% with stage 3 disease
  • 36.8% with stage 2 disease
  • Reference – Ocul Immunol Inflamm 2024 Jul;32(5):621
• See proposed staging system for classification by severity of Eales disease by clinical exam.
• vitreous hemorrhage (stage 3b) appears to be the most common clinical finding on initial exam in patients with Eales disease
  •  based on retrospective cohort study
  • 500 patients (mean age 30 years, 95% male) with 898 eyes with Eales disease were evaluated
  • mean follow-up 15.8 years (range 10-21 years)
  • bilateral Eales disease in 81%
  • clinical findings of Eales disease at initial examination (in order of frequency)
    • vitreous hemorrhage (stage 3b) in 41.2%
    • traction/combined rhegmatogenous retinal detachment (stage 4a) in 19.8%
    • neovascularization elsewhere or of the disc (stage 2b) in 18.2%
    • rubeosis iridis (neovascularization of iris), neovascular glaucoma, complicated cataract, and optic atrophy (stage 4b) in 7.7%
    • periphlebitis of small peripheral retinal capillaries (stage 1a) in 5.8%
    • periphlebitis of large caliber vessels (stage 1b) in 5.4%
    • fibrovascular proliferation (stage 3a) in 1.4%
    • peripheral capillary nonperfusion (stage 2a) in 0.3%
  • Reference – Ocul Immunol Inflamm 2018;26(6):870

Diagnosis

Making the Diagnosis

• Eales disease is diagnosed clinically after exclusion of other ocular conditions that can present with similar retinal features, including reduction in visual acuity and symptoms of recurrent vitreous hemorrhage (small specks, floaters, or cobwebs occluding the vision).^(1,2,3)
• Eales disease can be diagnosed in any of 3 overlapping phases of progressively worsening disease with an eye exam (venous inflammation [vasculitis], vascular occlusion, and retinal neovascularization), which can help guide management.^(1,3)
  • Early inflammatory phase:
    • Fundoscopic exam findings include midperipheral venous dilation, perivascular exudate, superficial retinal hemorrhages, and vascular sheathing.
    • Active vasculitis is indicated on fluorescein angiography by vessel wall staining or extravasation (inactive inflammation does not stain).
  • Intermediate ischemic phase:
    • Fundoscopic exam findings include solid white lines on areas of nonperfusion and highly distinct junction between anterior peripheral nonperfusion and posterior perfused retina.
    • Fluorescein angiography shows venous obstruction causing venous stasis, which is indicated by engorged tortuous veins distal to the obstruction and engorgement of the capillary bed.
  • Late proliferative phase:
    • Fundoscopic exam findings in patients with recurrent hemorrhage include evidence of old blood, signs of fibrous organization, retinitis proliferans, and tractional retinal detachment.
    • Neovascularization on fluorescein angiography is indicated by abnormal branching patterns and dye leak, which stops after resolution of venous inflammation.

Differential Diagnosis

• Ocular tuberculosis is infection of the eye with Mycobacterium tuberculosis.
  • The most common presentation is disseminated choroiditis with well-circumscribed lesions located deep in the choroid appearing yellow, white, or grey.
  •  Focal choroiditis may appear at the posterior pole.
  • Reference – Indian J Ophthalmol 2010 Jan;58(1):29full-text
• Other causes of retinal vasculitis include:⁽³⁾
  • Behcet syndrome
  • Pars planitis (inflammation of the intermediate uveitis)
  • Birdshot chorioretinopathy
  • Viral retinitis
  • Coats disease
  • Granulomatosis with polyangiitis
  • Leukemia
  • Lyme disease
  • Multiple sclerosis
  • Ocular syphilis
  • Sarcoidosis
  • Systemic lupus erythematosus
  • Toxoplasmosis
• Other causes of vascular retinopathy:⁽³⁾
  • Branch or central retinal vein occlusion
  • Coats disease
  • Pars planitis (inflammation of the intermediate uveitis)
  • Retinopathy of prematurity (ROP)
  • Diabetes mellitus type 1
  • Sarcoidosis
  • Sickle cell disease
• Other causes of tractional retinal detachment:
  • Sickle cell retinopathy
  • Retinal vein occlusion
  • Penetrating injury
  • Surgery
  • Infection
  • Inflammation due to proliferative diabetic retinopathy, proliferative vitreoretinopathy, or retinopathy of prematurity
  • Reference – BMJ 2008 May 31;336(7655):1235full-text

Testing Overview

• Blood tests may be useful for ruling out other causes of phlebitis, vascular occlusion, and retinal neovascularization, and may include:
  • Erythrocyte sedimentation rate and/or C-reactive protein
  • Complete blood count
  • Metabolic panel
  • Syphilis testing
  • HIV serology
• Testing for tuberculosis infection can assess exposure to Mycobacterium tuberculosis and hypersensitivity to tuberculoproteins, which are proposed causes of Eales disease. Testing may include:
  • QuantiFERON-TB Gold test (blood test) (reported to be positive in 56% of patients with Eales disease in cohort study)
  • Mantoux test (Tuberculin skin testing) (reported to be positive in 64%-73% of patients with Eales disease in 2 cohort studies)
• Fluorescein angiography may be used for assessing and monitoring retinal perfusion and identifying phlebitis.
• Other imaging studies may include:
  • Ophthalmic ultrasonography to assess retinal detachment in patients with opacity due to vitreous hemorrhage.
  • Optical coherence tomography for assessment of macular involvement.
• Urinalysis may be useful in ruling out other causes of retinal vasculitis (Middle East Afr J Ophthalmol 2009 Oct;16(4):202full-text).

Blood Tests

• Blood tests may be useful for ruling out other causes of phlebitis, vascular occlusion, and retinal neovascularization, and may include:
  • Erythrocyte sedimentation rate and/or C-reactive protein
  • Complete blood count
  • Metabolic panel
  • Syphilis testing
  • HIV serology
  • References – ⁽¹⁾, Middle East Afr J Ophthalmol 2009 Oct;16(4):202full-text
• Decisions for additional testing may be based on clinical findings of underlying systemic disease (Middle East Afr J Ophthalmol 2009 Oct;16(4):202full-text).

Imaging Studies

• Fluorescein angiography may be used for assessing and monitoring retinal perfusion and identifying phlebitis.
  • IV injection of fluorescein (yellow dye) and sequential photographs are used to assess choroidal and retinal blood flow and dye leakage into retinal tissues (hyperfluorescence).
  • Wide-field fluorescein angiography may be more useful for imaging of peripheral eye areas.
  • Findings on fluorescein angiography or wide-field fluorescein angiography indicating Eales disease include:
    • Active vasculitis, indicated by vessel wall staining or extravasation (inactive inflammation does not stain)
    • Venous obstruction causing venous stasis, indicated by engorged tortuous veins distal to the obstruction and engorgement of the capillary bed
    • Neovascularization, indicated by abnormal branching patterns and dye leak, which stops after resolution of venous inflammation
    • Deep choroiditis along the inflamed veins, which may be present throughout disease development and healing
  • References – ^(1,2,3), Lancet 2012 May 5;379(9827):1728, Arq Bras Oftalmol 2019 May 20;82(4):339
• ophthalmic ultrasound may be used to assess retinal detachment in patients with opacity due to vitreous hemorrhage limiting fundoscopic exam (Am Fam Physician 2004 Apr 1;69(7):1691full-text)
• optical coherence tomography (OCT) may be useful for assessment of the macula (Indian J Ophthalmol 2018 Mar;66(3):433full-text)
• chest x-ray may be used to assess for concomitant Mycobacterium tuberculosis infection (Indian J Ophthalmol 2018 Mar;66(3):433full-text)

Biopsy and Pathology

• Vitreous and epiretinal membrane sample collection for histology assessment may occur during vitrectomy.⁽³⁾
• Patients with Eales disease have similar vitreous composition as patients with other retinal vascular diseases but may show chronic inflammatory cell infiltration.⁽³⁾
  • Lymphocytic infiltration may be found around new vascular channels and within the epiretinal membrane.
  • Lymphocytes are primarily T cell, though B-cell type may be present.

Testing for Tuberculosis Infection

• Test for Tuberculosis infection using either QuantiFERON-TB Gold blood test or Mantoux test (tuberculin skin test) (^(1,2,3), Am Fam Physician 2021 Feb 1;103(3):177).
• Testing for tuberculosis infection can assess exposure to Mycobacterium tuberculosis and hypersensitivity to tuberculoproteins, which are proposed causes of Eales disease.⁽¹⁾
• EVIDENCE SYNOPSIS: Positive test for M. tuberculosis appears common in patients with Eales disease, reported in 64%-73% by Mantoux test and 56% by QuantiFERON-TB Gold blood test, and may be associated with lower visual acuity in patients with Eales disease.
  • positive test for M. tuberculosis appears common in patients with Eales disease (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    • 50 patients (mean age 35 years, 82% male) with 79 eyes with Eales disease were evaluated for M. tuberculosis
    • positive Mantoux test in 73% of 44 patients
    • positive QuantiFERON-TB Gold test (interferon gamma release assay) in 56% of 34 patients
    • chest high resolution computed tomography indicating pulmonary tuberculosis in 34% of 44 patients
    • Reference – Int Ophthalmol 2021 Mar;41(3):901
  • positive Mantoux test may be associated with lower visual acuity in patients with Eales disease (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    • 500 patients (mean age 30 years, 95% male) with 898 eyes with Eales disease were evaluated
    • mean follow-up 15.8 years (range 10-21 years)
    • bilateral Eales disease in 81%
    • positive Mantoux test (tuberculin skin test) in 64% of patients
    • tuberculosis was confirmed by a pulmonologist in 3% of patients
    • visual acuity lower in patients with positive Mantoux test compared to patients with negative Mantoux test (p = 0.0057)
    • Reference – Ocul Immunol Inflamm 2018;26(6):870

Staging

• Proposed staging system for classifying and assessing severity of Eales disease based on clinical findings of physiological disease phases.⁽²⁾
  • Inflammatory phase:
    • Stage 1a – periphlebitis of small peripheral retinal capillaries with superficial retinal hemorrhages
    • Stage 1b – periphlebitis of large caliber vessels with superficial retinal hemorrhages
  • Retinal ischemia and neovascularization phase:
    • Stage 2a – peripheral capillary nonperfusion
    • Stage 2b – neovascularization elsewhere in the retina or of the optic disc
  • Late proliferative phase:
    • Stage 3a – fibrovascular proliferation
    • Stage 3b – vitreous hemorrhage
  • Advanced disease with complications:
    • Stage 4a – traction/combined rhegmatogenous retinal detachment
    • Stage 4b – rubeosis iridis (neovascularization of the iris), neovascular glaucoma, complicated cataract, and optic atrophy
  • Reference – Eur J Ophthalmol 2004 May;14(3):236

Management

Management Overview

• Goals of management:^(1,3)
  • Limit retinal perivasculitis and vitritis
  • Reduce risk of vitreous hemorrhage due to retinal neovascularization
  • Remove nonresolving vitreous hemorrhage or vitreous membranes with vitrectomy
• Management varies by severity of Eales disease.
  • In patients with early inflammatory phase Eales disease, high-dose oral corticosteroids are first-line.
    • In patients refractory to corticosteroids or those with contraindications to corticosteroids or adverse effects, steroid-sparing immunosuppressives agents, such as cyclosporine and azathioprine, may be used.
    • In patients with positive tuberculosis skin test or acute phlebitis with massive infiltration, nodule formation, and total obliteration of vein segments, antitubercular treatment (given for 9 months) in combination with oral corticosteroids may be appropriate.
    • In patients with very active retinal vasculitis or central Eales disease with macular involvement, triamcinolone intravitreal injection may be appropriate.
  • In patients with intermediate ischemic phase Eales disease (retinal vein occlusion), antivascular endothelial growth factor (anti-VEGF) therapy may be appropriate.
  • In patients with late proliferation phase Eales disease, laser photocoagulation therapy is the primary treatment.
    • In those with elevated expression of VEGF, anti-VEGF therapy may be appropriate and may be combined with photocoagulation therapy or vitrectomy.
    • In patients with nonclearing vitreous hemorrhage after 3 months, multiple vitreous membranes, tractional retinal detachment, and/or rhegmatogenous (retinal detachment due to retinal tear), vitrectomy may be indicated.
• Timing of follow-up varies by severity of Eales disease.
  • In patients with recent vitreous hemorrhage and attached retina, follow-up with eye exam and ophthalmic ultrasound every 4-6 weeks.
  • In patients with inactive retinal vasculitis, follow-up with eye exam every 6-12 months.

Medications

Oral Medications

• High-dose corticosteroids are first-line therapy for patients in the early inflammatory phase of disease.^(1,2,3)
  • Prednisolone may be used for initial control of symptoms and tapered as vasculitis resolves.⁽³⁾
  • The suggested dose for prednisolone in patients with disorders of the eye ranges from 5 to 60 mg/day orally.
  • oral corticosteroids during acute phase may be associated with improved visual acuity in patients with Eales disease (level 2 [mid-level] evidence)
    •  based on retrospective cohort study
    • 500 patients (mean age 30 years, 95% male) with 898 eyes with Eales disease were evaluated
    • mean follow-up 15.8 years (range 10-21 years)
    • 85.4% of eyes were managed with oral corticosteroid
    • visual acuity measured using logarithm of minimum angle of resolution (LogMAR) chart
      • standard vision (20/20) indicated by score of 0
      • poor vision (20/25 to 20/200) indicated by positive score, ranging from 0.1 to 1
      • good vision (20/16-20/10) indicated by negative score, ranging from -0.1 to -0.3
    • mean visual acuity in patients who had oral corticosteroid during acute phase 0.42 LogMAR vs. 0.59 LogMAR in patients who did not have oral corticosteroid (p = 0.004)
    • Reference – Ocul Immunol Inflamm 2018;26(6):870
• In patients with a new positive tuberculosis skin test or acute phlebitis with massive infiltration, nodule formation, and total obliteration of vein segments, antitubercular treatment for 9 months, in combination with oral corticosteroids, may be appropriate.^(2,3)
• In patients refractory to corticosteroids or those with contraindications to corticosteroids or adverse effects, steroid-sparing immunosuppressive agents, such as cyclosporine and azathioprine, may be used.^(1,2)

Intravitreal Injections

• Triamcinolone acetonide 4 mg in 0.1 mL intravitreal injection once may be appropriate in patients with very active retinal vasculitis or central Eales disease with macular involvement.^(2,3)
  • Triamcinolone acetonide 4 mg per 0.1 mL intravitreal injection reported to reduce retinal leakage in 12 adults (10 eyes) with periphlebitis due to Eales disease in case series (Eye (Lond) 2007 Nov;21(11):1403).
  • Triamcinolone acetonide 4 mg/0.1 mL intravitreal injection reported to resolve persistent periphlebitis in 2 patients (3 eyes) with Eales disease refractory to oral corticosteroids in case series (Retina 2006 Feb;26(2):227).
• Vascular endothelial growth factor (VEGF), an inflammatory cytokine, is upregulated in eyes with vein occlusions and promotes vascular permeability and neovascularization (Asia Pac J Ophthalmol (Phila) 2018 Jan;7(1):40).
  • Antivascular endothelial growth factor (anti-VEGF) therapy may be appropriate in patients with elevated expression of VEGF due to either of the following:
    • Retinal vein occlusion during the intermediate ischemia phase (Asia Pac J Ophthalmol (Phila) 2018 Jan;7(1):40)
    • Neovascularization during the late proliferative phase⁽³⁾
  • Anti-VEGF therapy may be used in combination with photocoagulation therapy or vitrectomy.⁽³⁾
  • Anti-VEGF agent bevacizumab is reported to lead to regression of neovascularization and reduce vitreous hemorrhage.^(2,3)
    • Bevacizumab dose is 1.25 mg/0.05 mL intravitreal injection once monthly for 3 months (Pak J Med Sci 2018 Mar;34(2):333full-text).
    • EVIDENCE SYNOPSIS: Bevacizumab intravitreal injection may help reduce the risk of disease progression and need for vitrectomy in adults with early stage (stage 1 or 2) Eales disease but does not appear effective for more severe Eales disease (stage 3 or 4).
      • addition of bevacizumab intravitreal injection to standard therapy may decrease risk of disease progression in adults with stage 1 or 2 Eales disease (level 2 [mid-level] evidence)
        •  based on randomized trial without intention-to-treat analysis
        • 30 adults (mean age 28 years) with 60 eyes with stage 1 or 2 bilateral Eales disease were randomized to bevacizumab 1.25 mg /0.05 mL intravitreal injection once monthly for 3 months plus standard therapy vs. standard therapy alone
        • standard therapy included periocular or intravitreal triamcinolone injection with peripheral laser photocoagulation and topical pressure lowering treatment
        • 52 eyes of 26 patients were included in analysis after 4 patients were lost to follow-up
        • comparing bevacizumab plus standard therapy vs. standard therapy alone at 12 weeks
          • progression to stage 3 or 4 Eales disease in 34.6% vs. 69.2% (p = 0.012, NNT 3)
          • pars plana vitrectomy for nonresolving vitreous hemorrhage or retinal detachment in 23% vs. 61.5% (p = 0.005, NNT 3)
          • regression in neovascularization in 61.5% vs. 23.1% (p = 0.005, NNT 3)
        • Reference – Pak J Med Sci 2018 Mar;34(2):333full-text
      • bevacizumab intravitreal injection may not hasten resolution of vitreous hemorrhage or risk of vitrectomy in male adults with severe vitreous hemorrhage due to Eales disease (level 2 [mid-level] evidence)
        •  based on small randomized trial
        • 20 male adults with 20 eyes with vitreous hemorrhage due to Eales disease were randomized to bevacizumab 1.25 mg/0.05 mL intravitreal injection once monthly vs. observation and followed every 2 weeks for 3 months
        • all patients had severe vitreous hemorrhage defined as grade 3 (red reflex is present, with no retinal detail seen posterior to the equator) or grade 4 (dense vitreous hemorrhage with no red reflex present) on vitreous hemorrhage grading scale
        • no significant differences between groups in
          • resolution of vitreous hemorrhage or risk of vitrectomy at 3-month follow-up
          • postoperative visual acuity at 1-month follow-up
          • risk of tractional retinal detachment at 2-week follow-up
        • Reference – Retina 2011 May;31(5):866
    • severe Eales disease appears to be associated with secondary rhegmatogenous retinal detachment within 1 week of bevacizumab intravitreal injection (level 3 [lacking direct] evidence)
      •  based on prospective cohort study
      • 14 men (median age 33 years) with severe Eales disease were given bevacizumab 1.25 mg/0.05 mL intravitreal injection 3-7 days prior to vitrectomy and followed for 3 months
        • 50% of patients had vitreous hemorrhage
        • 50% of patients had vitreous hemorrhage and tractional retinal detachment
      • median duration of vitreous hemorrhage 5 months
      • 28.6% of patients had secondary rhegmatogenous retinal detachment within 1 week of bevacizumab intravitreal injection
      • secondary rhegmatogenous retinal detachment in patients with vitreous hemorrhage and tractional retinal detachment in 43% vs. 14.3% in patients with vitreous hemorrhage (not significant)
      • Reference – Graefes Arch Clin Exp Ophthalmol 2012 May;250(5):685
• Other options for intravitreal injection used in case reports:
  • Ranibizumab 0.5 mg intravitreal injection once monthly for 3 months reported to transiently reduce macular edema at 3 months in 77-year-old female with central Eales disease in case report (Retin Cases Brief Rep 2012 Winter;6(1):122).
  • Multiple aflibercept 2 mg/0.05 mL intravitreal injections reported to regress retinal neovascularization in 2 patients with recurrent Eales disease in case series (Case Rep Ophthalmol Med 2021;2021:8887362full-text).
• In general, potential adverse effects of intravitreal injections include:
  • Ocular hemorrhage
  • Increased intraocular pressure
  • Infectious endophthalmitis
  • Noninfectious inflammatory reactions
  • Increased retinal traction and consequent detachment
  • Rhegmatogenous retinal detachment
  • Possible systemic effects of the agent
  • Cataract formation
  • Reference – American Academy of Ophthalmology (AAO): Diabetic Retinopathy Preferred Practice Pattern – Updated 2019 (AAO 2019 Oct)

Surgery and Procedures

Laser Photocoagulation Therapy

• Laser photocoagulation is the primary treatment for patients with Eales disease in the late proliferation phase .^(1,2,3)
• Options include:⁽³⁾
  • Focal laser therapy of flat retinal new vessels
  • Sectoral scatter photocoagulation of capillary nonperfusion area
  • Direct treatment of neovascular frond into the vitreous
• Fluorescein angiography may be used to monitor treatment response.^(2,3)
• Photocoagulation is not indicated in patients with active vasculitis as it may increase angiogenic factors that could worsen neovascularization (Case Rep Ophthalmol Med 2021;2021:1056659).
• laser photocoagulation therapy may improve visual acuity in patients with Eales disease (level 2 [mid-level] evidence)
  •  based on retrospective cohort study
  • 500 patients (mean age 30 years, 95% male) with 898 eyes with Eales disease were evaluated
    • 78% of eyes were managed with laser therapy (laser photocoagulation, pan retinal photocoagulation, or endolaser therapy)
    • 22% of eyes were not managed with laser therapy
  • mean follow-up 15.8 years (range 10-21 years)
  • visual acuity measured using logarithm of minimum angle of resolution (LogMAR) chart
    • standard vision (20/20) indicated by score of 0
    • poor vision (20/25 to 20/200) indicated by positive score, ranging from 0.1 to 1
    • good vision (20/16-20/10) indicated by negative score, ranging from -0.1 to -0.3
  • mean visual acuity in patients who had laser therapy at the final visit 0.41 LogMAR vs. 0.92 LogMAR in patients who did not have laser therapy (p < 0.001)
  • Reference – Ocul Immunol Inflamm 2018;26(6):870
• prophylactic laser photocoagulation therapy to asymptomatic eyes with signs of Eales disease may improve visual acuity and limit persistent vitreous hemorrhage (level 2 [mid-level] evidence)
  •  based on randomized trial without blinding
  • 99 patients (mean age 28 years) with Eales disease had oral corticosteroids and laser photocoagulation or vitrectomy in symptomatic eye
  • 86 patients had signs of disease in the asymptomatic eye and were randomized to prophylactic laser photocoagulation therapy every 3-4 weeks for 2-3 session vs. no laser photocoagulation therapy and followed every 6 months for 3 years
    • comparing laser photocoagulation therapy vs. no laser photocoagulation therapy at 3-year follow-up
      • improved visual acuity in 90.7% vs. 20.9% (p < 0.005, NNT 1)
      • persistent vitreous hemorrhage in 37.2% vs. 76.7% (p < 0.005, NNT 2)
      • regressive fundus changes in 69.8% vs. 34.9% (p < 0.005, NNT 3)
    • adverse events reported in patients who had laser photocoagulation therapy
      • postprocedural pain in 34.9%
      • preretinal hemorrhage in 16.3%
      • vitreous rebleed in 13.9%
      • choroidal neovascular membrane formation in 7%
  • Reference – J Ayub Med Coll Abbottabad 2002 Oct;14(4):22

Vitrectomy

• Pars plana vitrectomy surgery may be used to repair or reattach torn retina and replace cloudy vitreous (National Eye Institute 2020 Dec 23).
• Vitrectomy may be indicated in patients with:^(1,3)
  • Nonclearing vitreous hemorrhage after 3 months
  • Tractional retinal detachment involving the posterior pole
  • Multiple vitreous membranes
  • Combined rhegmatogenous (retinal detachment due to retinal tear) and tractional retinal detachment
• Postoperative complications of vitrectomy may include:^(2,3)
  • Vitreous hemorrhage
  • Cataract
  • Secondary glaucoma
  • Rhegmatogenous retinal detachment
• Additional procedures, such as laser photocoagulation therapy, scleral buckle, and lensectomy may be performed at the same time as vitrectomy.^(2,3)
• vitrectomy reported to improve visual acuity in most patients with Eales disease and nonresolving vitreous hemorrhage or retinal detachment (level 3 [lacking direct] evidence)
  •  based on case series
  • 21 adults (mean age 34 years, 90% men) with 22 eyes with Eales disease had vitrectomy for nonresolving vitreous hemorrhage or tractional and/or rhegmatogenous retinal detachment
  • mean follow-up 67.8 months
  • anatomic surgical success achieved in 90.9% of eyes (anatomic surgical success not explicitly defined)
  • mean preoperative best corrected visual acuity 1.8 LogMAR vs. 0.6 LogMAR postoperatively (p < 0.001)
  • recurrent or new retinal detachment requiring revision surgery in 4 eyes
  • Reference – Turk J Ophthalmol 2021 Apr 29;51(2):102full-text

Follow-up

• In patients with recent vitreous hemorrhage and attached retina:⁽²⁾
  • Follow-up with eye exam and ophthalmic ultrasound every 4-6 weeks.
  • Vitreous hemorrhage will likely resolve at 6-8 weeks.
• In patients with inactive retinal vasculitis, follow-up with eye exam every 6-12 months.⁽²⁾

Complications

• Complications of Eales disease may include:⁽³⁾
  • Uveitis
  • Complicated cataract
  • Retinal detachment
  • Rubeosis iridis (neovascularization of iris)
  • Neovascular glaucoma
  • Macular edema
  • Vitreous hemorrhage
• Neurological complications, such as stroke, seizure, nonspecific white matter changes, and myelopathy have been reported (Ann Indian Acad Neurol 2020 Jul;23(4):563full-text).
• about 25% of eyes treated for Eales disease may develop ≥ 1 complications during long-term follow-up, most commonly macular edema
  •  based on retrospective cohort study
  • 500 patients (mean age 30 years, 95% male) with 898 eyes treated for Eales disease were evaluated
  • eyes were treated with ≥ 1 of the following
    • laser photocoagulation in 78%
    • oral corticosteroids in 72.6%
    • pars plana vitrectomy in 26.4%
    • scleral buckle and vitrectomy in 21.5%
    • corticosteroid periocular injection in 12.8%
    • triamcinolone intravitreal injection in 2%
  • mean follow-up 15.8 years (range 10-21 years)
  • complications in 24.6% of eyes
    • macular edema in 20.8%
    • neovascularization of the iris in 12.2%
    • secondary glaucoma in 12.2%
    • epiretinal membrane in 11.7%
    • neovascular glaucoma in 10.4%
    • complicated cataract in 9%
    • phthisis bulbi (end-stage eye disease characterized by shrinkage and disorganization of the eye with the resultant functional loss) in 5.4%
    • macular exudates in 4.1%
  • Reference – Ocul Immunol Inflamm 2018;26(6):870

Prognosis

• The clinical course of Eales disease is highly variable, with some patients progressing to complete vision loss and others experiencing temporary or permanent remission.⁽³⁾
• Individual episodes of vitreous hemorrhage typically resolve at 6-8 weeks.⁽²⁾
• Vision loss is most commonly due to recurrent vitreous hemorrhage.⁽²⁾
• 52% of eyes had < 5 recurrences over a 10-year follow-up period in retrospective cohort of 500 patients (898 eyes) with Eales disease (Ocul Immunol Inflamm 2018;26(6):870).
• poor visual acuity and disease stage 4a at time of presentation may each be associated with poor visual acuity at long-term follow-up in patients with Eales disease
  •  based on retrospective cohort study
  • 500 patients (mean age 30 years, 95% male) with 898 eyes with Eales disease were evaluated
  • mean follow-up 15.8 years (range 10-21 years)
  • 81% of patients had bilateral Eales disease at initial presentation
  • 25% of patients with unilateral Eales disease at initial presentation developed bilateral disease over follow-up
  • factors associated with increased risk for poor visual acuity at final follow-up
    • poor presenting visual acuity (odds ratio 3.67, 95% CI 2.96-4.53)
    • stage 4a stage of disease at presentation (odds ratio 8.06, 95% CI 2.41-26.99)
  • Reference – Ocul Immunol Inflamm 2018;26(6):870

Prevention and Screening

• Not applicable.

Guidelines and Resources

Guidelines

• No relevant guidelines for “Eales Disease” found 2024 Dec 8 on MEDLINE search using guidelines limiter.

Review Articles

• Reviews can be found in:
  • Biology (Basel) 2024 Jun 20;13(6)full-text
  • J Fr Ophtalmol 2016 May;39(5):474 [French].
  • J Ophthalmic Inflamm Infect 2013 Jan 14;3(1):11.
  • Eye (Lond) 2010 Mar;24(3):472.
• Review of a multidisciplinary approach to the management of Eales disease can be found in J Pers Med 2024 Feb 22;14(3)full-text

MEDLINE Search

• To search MEDLINE for (Eales Disease) with targeted search (Clinical Queries), click therapy, diagnosis, or prognosis.

Patient Information

• Handout from National Organization for Rare Diseases
• Handout on vitreous hemorrhage from Patient UK PDF

References

General References Used

1. Biology (Basel) 2024 Jun 20;13(6)full-text.
2. Biswas J, Ravi RK, Naryanasamy A, Kulandai LT, Madhavan HN. Eales’ disease – current concepts in diagnosis and management. J Ophthalmic Inflamm Infect. 2013 Jan 14;3(1):11full-text.
3. Das T, Pathengay A, Hussain N, Biswas J. Eales’ disease: diagnosis and management. Eye (Lond). 2010 Mar;24(3):472-82.